This program project is a composite of four separate studies designed to explore in a highly integrated, multidisciplinary fashion, certain fundamental issues regarding the clinical and basic science of human immunodeficiency virus (HIV)- related neurological disease. The key study is a longitudinal study of asymptomatic, HIV seropositive individuals and sex, age and AIDS risk group matched controls for the development of neurological disease utilizing multiple parameters of assessment. Among the issues that will be addressed are the frequency with which neurological disease develops in association with HIV infection, the natural history of these disorders, and the identification of predictors for their development. Detailed clinical and laboratory evaluation of the study subjects with cerebrospinal fluid (CSF) analysis will allow us to explore the relationship of HIV-related neurological disease to the presence of HIV and the nature of the immune response to HIV, the presence of cytomegalovirus (CMV) and the nature the immune response to CMV, and the presence of brain reactive antibody.